Functional brain imaging has the potential to advance the diagnosis and treatment of major neuropsychiatric illness as well as contribute to the understanding of its causes. This potential has remained unfulfilled because of technological impediments that can be surmounted by construction of infrastructure to facilitate sharing of data such as federated databases and information discovery tools based on knowledge engineering approaches. This Functional Imaging Research in Schizophrenia Testbed (FIRST) BIRN proposal, in response to the NCRR "Biomedical Imaging Research Network" RFA, focuses upon the development and validation of a common fMRI protocol for a large-scale multi-center study of schizophrenia. The proposal is crystallized around a high-speed broadband network supporting a federated database, specifically developed for the pooling and sharing of data across sites to facilitate large scale hypothesis testing and intelligent data mining to address complex scientific problems. There are two major goals. The first goal is technological - development of a distributed network infrastructure that will support the creation of a federated database consisting of large-sample fMRI datasets contributed by the eleven institutions at ten centers. To meet this goal, the consortium will assess the major sources of variation in fMRI studies conducted across centers, including instrumentation, calibration, acquisition protocols, challenge tasks, and analysis methods, and develop methods that support the analysis of a combined data set. The second major goal is clinical -applying the technology developed in this proposal to study specific regional brain dysfunction, as well as changes in brain function in the progression and treatment of schizophrenia. In addition, this proposal specifically intends to capture the added value of each center's unique approach to the study of schizophrenia in their currently funded projects. These independent projects use diverse fMRI cognitive activation tasks and study unique patient populations. In this proposal, a common consortium fMRI protocol will be standardized, calibrated, and validated to enhance sharing of data across sites and populations. The infrastructure and federated database developed in this proposal will provide access to and sharing of stored MRI images, clinical findings, and behavioral data relevant to the study of schizophrenia. The technology and infrastructure developed by this proposal, using advances in information engineering and broadband networking, will create a federated database focused on sharing data and intelligent database querying to address the proposal hypotheses and generate new knowledge. The technological developments supported by this proposal will accelerate progress in understanding and treating schizophrenia and be immediately applicable to other disorders.